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Behavioral interactions between muscimol and compounds selective for the D1 and D2 dopamine receptor subtypes.

The present study investigated the effects of the GABA agonist muscimol on the behaviors produced by acute injections of selective D1 and D2 agonists and antagonists. Muscimol potentiated the intensity of stereotyped behaviors shown by rats treated with the D2 agonist quinpirole; in contrast, it suppressed the repetitive bouts of grooming shown by rats treated with SKF38393. Muscimol potentiated the catalepsy produced by either a D1 (SCH23390) or D2 (metoclopramide) antagonist, suggesting that the cataleptic behaviors produced by these compounds may contain a common GABAergic mechanism.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

The effects of cholinergic agents on morphine-induced circling behavior in the intact mouse.

The effects of morphine on locomotor activity in mice was studied. It was shown that morphine in this species induces circling, a dose-dependent, stereotyped behavior. At high doses of morphine, mice engaged virtually exclusively in circling uninterrupted by other activities. The effect was modified by muscarinic agents. Blockade of muscarinic receptors with atropine potentiated circling while the muscarinic agonist, oxotremorine, attenuated it. The mixed muscarinic/nicotinic cholinergic agonist, physostigmine, had no effect on this behavior.

Animals↗

Behavioral variability and frequency-dependent selection.

In Experiment 1, two conditions were compared: (a) a variability schedule in which food reinforcement was delivered for the fourth peck in a sequence that differed from the preceding N four-peck sequences, with the value of N continuously adjusted to maintain reinforcement probability approximately constant; and (b) a control condition in which the variability constraint was dropped but reinforcement probability remained constant. Pigeons responded approximately randomly under the variability schedule but showed strong stereotyped behavior under the control condition. Experiments 2 and 3 tested the idea that variability is the outcome of a type of frequency-dependent selection, namely differential reinforcement of infrequent behavior patterns. The results showed that pigeons alternate when frequency-dependent selection is applied to single pecks because alternation is an easy-to-learn stable pattern that satisfies the frequency-dependent condition. Nevertheless, 2 of 4 pigeons showed random behavior when frequency-dependent selection was applied to two pecks, even though double alternation is a permissible and stable stereotype under these conditions. It appears that random behavior results when pigeons are unable to acquire the stable stereotyped behavior under a given frequency-dependent schedule.

Animals↗

Ibotenic acid lesions of prefrontal cortex do not prevent expression of behavioral sensitization to amphetamine.

We have shown previously that ibotenic acid lesions of the prefrontal cortex, performed prior to repeated amphetamine administration, do not affect sensitization of stereotyped behaviors but do prevent sensitization of post-stereotypy locomotor hyperactivity [Wolf et al., Neuroscience, 69 (1995) 417-439]. This could reflect an effect of the lesion on either development or expression of locomotor sensitization. To test the latter possibility, rats were treated with repeated amphetamine injections and tested to establish behavioral sensitization. Then, half received ibotenic acid lesions of prefrontal cortex and half received sham lesions. A second amphetamine challenge, 7 days later, demonstrated that the lesion failed to prevent expression of sensitization. Together with previous results, this suggests that intrinsic neurons of prefrontal cortex, most likely those sending excitatory amino acid-containing projections to the ventral tegmental area, are required for the development but not the expression of behavioral sensitization to amphetamine.

Amphetamine↗

Comparison of behavior and performance of laying hens housed in battery cages and an aviary.

Experiments were carried out to study the behavior and production performance of hens housed in battery cages (3 birds x 112 cages) and an aviary (437 birds). Direct visual observations and videotapings of hen behavior were collected at 24 to 25, 36 to 37, 49 to 50, and 61 to 62 wk of age. Production data were collected daily. Stereotyped behaviors were much more frequent (P less than .01) in the battery cages (7.0 to 24.7%) than in the aviary (1.0 to 2.7%). Comfort behaviors were performed by aviary birds (3.9 to 5.5%) much more frequently (P less than .01) than by the caged birds (.7 to .9%). The birds were more active during a few hours before dark and just after light in both cages and the aviary. In both groups, the production performance of hens was similar and relatively high. The results of the current study indicate that aviaries provide a more comfortable environment for birds and almost the same productivity per bird as battery cages.

Age Factors↗

Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats.

d-Amphetamine and phencyclidine (PCP) have both been reported to produce manic-like sequela in humans, effects that are reportedly antagonized by lithium. To test the hypothesis that the acute effects of these drugs in rats may serve as models of mania, the behaviors induced by d-amphetamine (3 mg/kg) or PCP (5 mg/kg) were quantified on behavioral rating scales subsequent to chronic dietary pretreatment with lithium carbonate or control diet. On day 14 of pretreatment, PCP-induced stereotyped behaviors and ataxia were potentiated in rats receiving lithium (plasma levels 1.0 +/- 0.23 mEq/l). PCP-induced locomotor activity was not affected by lithium pretreatment. Stereotypies and locomotion induced by d-amphetamine were also not significantly affected by lithium pretreatment. These results suggest that neither PCP nor amphetamine administered acutely to rats will be useful models to explore the manic-like symptoms produced by these drugs in humans.

Animals↗

Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatment.

Rats were used in a study of the effects of repeated methamphetamine treatment on stereotyped behavior and striatal and limbic dopamine metabolism in response to challenge with the drug or other dopamine agonists. Repeated administration of d-methamphetamine (6 mg/kg per day for 3-14 days) produced long-term behavioral sensitization (augmented response to a challenge injection) not only to the compound (at 44-89 days after drug withdrawal) but also to apomorphine and nomifensine. Even a single injection of d-methamphetamine (6 mg/kg) enhanced the behavioral response to the drug. A challenge dose of d-methamphetamine (2 mg/kg) markedly increased dopamine turnover (lower dopamine and higher 3,4-dihydroxyphenylacetic acid levels, higher ratios of 3,4-dihydroxyphenylacetic acid over dopamine) in the striatum and mesolimbic area of the sensitized animals on day 15 of withdrawal from treatment repeated for 14 days with the drug (6 mg/kg per day). These findings demonstrate that behavioral sensitization induced by methamphetamine is accompanied by increased central dopaminergic transmission.

3,4-Dihydroxyphenylacetic Acid↗

Brain locations controlling the behavioral effects of chronic amphetamine intoxication.

Rats were administered D-amphetamine repeatedly for 4 days. After day 1 of treatment, the amphetamine-induced increases in ambulation, rearing, and stereotyped activity were augmented. However, after 4 days treatment, the rearing and ambulatory responses became attenuated while the stereotyped activities remained augmented. Micro-injection studies revealed that both the augmentation and attenuation of nonstereotyped ambulation were generated from the nucleus accumbens. The augmentation of stereotyped behaviors was generated from the caudate nucleus. Chronically treated animals who were administered 0.7 but not 1.0 mg/kg apomorphine showed augmented behavioral response. Chronic amphetamine treatment significantly decreased (3H) spiroperidol binding in both the nucleus accumbens and caudate nucleus. However, no effect on the DA-stimulated adenyl cyclase activity was observed in either brain region. It is concluded that repeated D-amphetamine administration selectively augments and attenuates D-amphetamine-induced behaviors and that these selective effects are mediated by different dopamine systems.

Adenylyl Cyclases↗

[Clinical subtypes of frontotemporal dementia].

Three distinctive clinical presentations can occur in frontotemporal dementia (FTD): disinhibited, apathetic and stereotypic subtypes. Each one shows a specific pattern of clinical, neuropsychological and neuroimaging findings, besides manifesting the core features of this form of dementia. We report three clinical cases, each one an example of a subtype of FTD, that were evaluated by neuropsychological and neuroimaging methods. Even the reported cases being a prototype of a specific subgroup, they can share some features with the others subtypes. According to this, patients with predominantly disinhibited or stereotypic behavior can also show apathy, in much the same way as predominantly apathetic or disinhibited patients can manifest stereotypic ritualistic behavior. The final stage of FTD is generally dominated by apathetic behavior.

Dementia↗

Effects of single and long-term administration of nifedipine on dopamine-related behaviors.

The effects of single (2.5 and 5.0 mg/kg) and long-term (2.5 mg/kg, twice daily, for 30 days) ip administration of nifedipine on open-field and apomorphine-induced stereotyped behavior were evaluated in young male Wistar rats (12-16 animals per group for the open-field studies and 7 animals per group for the stereotypy experiments). Administration of a single dose of nifedipine produced no changes in ambulation or rearing frequencies or in immobility duration in the open-field compared to controls. Similarly, treatment with a single dose of nifedipine did not modify apomorphine-induced stereotypy. Withdrawal from long-term nifedipine administration caused a significant increase only in rearing frequency 24 h after the last drug injection (with a mean +/- SEM frequency of 23.2 +/- 2.8 for the nifedipine group and of 14.7 +/- 2.0 for control rats, after 6-min observation). This enhancement of rearing frequency was no longer observed 48 h after abrupt nifedipine withdrawal (means +/- SEM: 15.0 +/- 2.2 and 19.6 +/- 2.7 for nifedipine-treated and control rats, respectively). The other open-field behavioral parameters and apomorphine-induced stereotypy (which was observed 96 h after nifedipine withdrawal) were not affected by long-term nifedipine treatment; for example, the sum of stereotypy scores (mean +/- SEM) was 26.9 +/- 3.0 for nifedipine-treated rats and 25.5 +/- 2.2 for vehicle-treated animals. The possible mechanisms underlying these results are discussed in light of the changes in dopaminergic neurotransmission induced by dihydropyridine calcium channel blockers.

Animals↗

Comparison of oral and subcutaneous routes of cocaine administration on behavior, plasma drug concentration and toxicity in female rats.

Oral and subcutaneous routes of administration of cocaine HCl were investigated in female Wistar rats for food and water consumption, locomotor activity, stereotypic behaviors, plasma drug concentrations and injection site pathology. Animals received either 40 or 80 mg/kg/day by gastric intubation (PO-40 and PO-80 respectively) or 20 or 40 mg/kg/day subcutaneously (SC-20 and SC-40). All groups received the drug or the vehicle for 16 consecutive days. Locomotor activity and stereotypy were evaluated on Days 1, 5, 10, and 15. Plasma drug concentrations and injection site pathology were determined on Day 16. Subcutaneous administration was associated with a sensitization to the effects of cocaine on locomotion and stereotypy, higher blood levels than oral administration at the same dose, and severe dermal lesions. However, there were no differences in any measure between the SC-20 and SC-40 groups. Oral cocaine was also associated with behavioral sensitization. However, unlike the SC route, oral cocaine was characterized by dose-related increases in locomotion and stereotypy in the absence of gastrointestinal pathology. Inasmuch as oral administration resulted in dose-response relationships and low toxicity while subcutaneous administration did not, these factors should be considered in future studies utilizing chronic cocaine administration.

Administration, Oral↗

Striatal c-fos levels do not correlate with haloperidol-induced behavioral supersensitivity.

Striatal c-fos levels and stereotyped behavior have been evaluated in chronically haloperidol-treated rats which received subsequent subacute dopamine (DA) agonist treatment to investigate the possible relationship between striatal c-fos and behavioral supersensitivity. Haloperidol treatment (1 mg/kg/day for 21 days) increased apomorphine-induced stereotypies but did not modify striatal c-fos levels. The subacute administration of the DA D-1 agonist SKF38393 (10 mg/kg/day for 5 days) and the combination of the D-1 agonist with the D-2 agonist quinpirole (1 mg/kg/day for 5 days) attenuated apomorphine-induced stereotypies after haloperidol pretreatment. The administration of quinpirole alone, however, did not modify the response to haloperidol. All DA agonists significantly increased c-fos levels after apomorphine injection. The dissociation between haloperidol-induced behavioral supersensitivity and striatal c-fos levels observed in this study suggests that mechanisms different from striatal c-fos induction might be involved, and that striatal c-fos levels are not a good marker of behavioral supersensitivity expression.

Animals↗

The effects of cocaine on multivariate locomotor behavior and defecation.

The present study utilized a multifactorial open-field analysis (Digiscan activity) to assess behavioral changes induced by various doses of cocaine known to stimulate locomotion. The measures that were implemented included ambulation, rearing, stereotypic behavior, rotational movements and changes in defecation levels. Thirty-two male Sprague-Dawley rats were habituated to Digiscan-16 Animal Activity Monitors (Omnitech Electronics, Columbus, OH) before being injected with 0.0, 10, 20 or 30 mg/kg cocaine. Rats were kept on a reversed light/dark schedule and tested in the middle of the dark cycle. It was found that cocaine consistently increased activity measures; most prominently affecting the rotational and ambulatory indices. Interestingly, this 'activity print' appeared to be dose-dependent and specific to cocaine. Open-field defecation levels were compared to home-cage levels as an additional behavioral correlate. Defecation decreased under all doses of cocaine as compared to control levels (saline injection). This result is attributed to cocaine's weakly sympathomimetic effect.

Animals↗

Autism and autistic behavior in Joubert syndrome.

To determine whether individuals with Joubert syndrome exhibit features of autism as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we examined 11 children with Joubert syndrome using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. Three children met DSM-IV criteria for autistic disorder and one for pervasive developmental disorder not otherwise specified. The other seven all demonstrated at least one DSM-IV symptom of autism, but did not meet criteria for a pervasive developmental disorder. Both total number of DSM-IV symptoms and number of social symptoms distinguished the autism and nonautism subgroups. In contrast, the two subgroups displayed similar levels of communication impairments and repetitive or stereotyped behavior. The key to diagnosing autism in Joubert syndrome is to focus on social behaviors, particularly milestones typically achieved very early in life (eg, attending to human voices, showing objects of interest, enjoyment of social interactions). Implications for the role of the cerebellum in nonmotor behavior and for clinical management of Joubert syndrome also are discussed.

Adolescent↗

Alterations in apomorphine concentration in spinal cord and brain follow the time course of catalepsies induced by different treatments.

Because evidence for the neurotransmitter role of dopamine in the gray matter of the spinal cord is accumulating, a question arises of whether or not spinal dopamine receptors are also involved in the effects of dopaminomimetics which are believed to induce beneficial effects in Parkinson's disease through an action thought to be mediated mainly by striatal dopamine receptors. To test this hypothesis muscimol and picrotoxin were injected unilaterally into the posterior part of the substantia nigra of rabbits permanently implanted with stainless-steel cannulae. Muscimol (a GABA-mimetic) enhanced locomotor activity, evoked a stereotyped behavior and contralateral rotations, and increased apomorphine-induced gnawing. Picrotoxin, a substance which inhibits GABA transmission, induced ipsilateral rotations, evoked catalepsy and muscle rigidity, and inhibited locomotor activity. Picrotoxin abolished apomorphine-induced gnawing, and increased haloperidol-mediated catalepsy. The catalepsy induced by an intranigral injection of picrotoxin, and the picrotoxin-evoked blockade of the apomorphine-induced gnawing disappeared within 16 h after the intranigral injection. Alterations in the apomorphine concentration in brain structures (n. caudatus and cerebral cortex) and in spinal cord after picrotoxin injection followed the same time course as the behavioral changes, and returned to the control values 16 h after injection of picrotoxin. Apomorphine was always injected 30 min before the rabbits were killed. Moreover, the substantial increase (to 300%) in apomorphine concentration in the spinal cord probably reflects the antagonism between behavioral changes induced by picrotoxin and the haloperidol catalepsy, rather than the decreased apomorphine concentrations observed in the brain structures. We suggest, therefore, that there exists a correlation between the behavioral effects, which are generally accepted as laboratory models of Parkinson's disease, and the enhanced apomorphine concentration in the spinal cord.

Animals↗

Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical?

The improved "attention" exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behavior. Such activity can be conceptualised as an increased "focusing" of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms.

Amphetamines↗

Ontogenesis of rearing and stereotypy responses to apomorphine in the rat.

The ontogenesis of rearing and stereotype behavior in response to apomorphine were investigated in the developing rat. The rearing was rarely observed in 15-day-old rats but distinctly in 18-day-old ones. A subcutaneous injection of apomorphine in dose of 1 mg/kg or 2 mg/kg decreased the frequency of rearing in older animals than day 20. On the other hand, 15-day-old rats were already responsive to apomorphine in stereotypy behavior. There was a reciprocal relationship between rearing and stereotypy responses to apomorphine in rat older than 18 days. Functional relationship between rearing and stereotypy in response to apomorphine were discussed in view of the central dopaminergic mechanisms in developing rats.

Age Factors↗

Differential behavioral activities from anterior and posterior hypothalamic lesions in the rat.

Bilateral 6-hydroxydopamine injections into the anterolateral (AL) or posterolateral (PL) portions of the hypothalamus produced hypokinesia, catalepsy, rigidity and severe weight losses due to aphagia and adipsia. Subcutaneous administration of apomorphine, 1 mg/kg, 48 hr after 6-OHDA injections reversed temporarily the hypokinesia in both AL and PL 6-OHDA groups. However, qualitative and quantitative differences in the behavioral responses to the drug were observed. Motor activity as measured by photocell counts was significantly greater in AL 6-OHDA rats. Apomorphine induced stereotyped behavior in both groups; however, the predominant behavioral responses were oral stereotypies in PL 6-OHDA animals and sniffing in AL 6-OHDA rats.

Animals↗